Elucidating the structure and function of the divergent and essential cytochrome bc1 complex in apicomplexan parasites

Apicomplexans parasites infect humans and cause fatal disease including malaria. To grow and transmit between people the parasite relies on its energy producing compartment, the mitochondrion, and the chain of electron-transferring protein-complexes needed for energy production. One complex, cytochrome bc1, is the target of several drugs, but their mechanism of action is poorly understood. I have recently analysed the protein composition of cytochrome bc1 in the apicomplexan parasite Toxoplasma, and found there are differences from the human complex. This provides clues about how the parasite complex is different from the human complex, but critical details need to be further investigated. I aim to use genetic manipulation and structural analysis to understand the differences in how apicomplexan versus human cytochrome bc1 complex functions, and precisely how the parasite complex binds to inhibitor drugs. My work will enhance our understanding of these divergent organisms' biology and may help develop new anti-parasitic drugs.